Cell death by apoptosis is a fundamental component of osteoblast differentiation that contributes to maintaining tissue organization. Evidence suggests that cells differentiating to the mature bone cell phenotype undergo programmed cell death and express genes regulating apoptosis. Despite a few studies, the detailed mechanism of apoptosis during bone remodeling is under explored. Osteoblasts (the cell responsible for bone deposit) and osteoclasts (responsible for resorption of bone) are responsible for the remodeling of bone and response to a large number of varied influences. Some of these are mechanical and others are growth factors or hormonal. Recent studies from Dr. McCauley's laboratory suggest that PTH (parathyroid hormone) and PTHrP (PTH related protein) exert both pro and anti apoptotic effects in mesenchymal cells. Both of these actions occur at least in part via the protein kinase A pathway. It has been also shown that the anabolic actions of PTH are dependent on the differentiation stage of the osteoblast. These suggest that a unique cell cycle control is instituted which is mechanistically different from that operative in pre confluent cultures and is sensitive to regulatory molecules, such as PTH. In the present application the cell cycle control mechanism of bone formation will be investigated with special emphasis on p53, a regulator of apoptosis (which controls transcription of Bax that influences mitochondrial permeability and the release of cytochrome C), using PTH treated MC3T3 osteoblastic cells.